Abstract:
:Although fluoride is known to stimulate bone formation, the underlying mechanisms are not fully understood. Recent studies have implicated the Wnt/β-catenin pathway as a major signaling cascade in bone biology. Our earlier studies highlighted a probable role of canonical Wnt pathway in bone formation of chronic fluoride-exposed rats, but the mechanism remains unclear. The current study determined the involvement of Wnt/β-catenin signaling in fluoride-induced osteoblastic differentiation. Using primary rat osteoblasts, we demonstrated that fluoride significantly promoted osteoblasts proliferation and alkaline phosphate (ALP) expression as well as the mRNA expression levels of bone differentiation markers, including type I collagen (COL1A1), ALP and osteonectin. We further found fluoride induced phosphorylations at serine 473 of Akt and serine 9 of glycogen synthase kinase-3β (GSK3β), which resulted in GSK-3β inhibition and subsequently the nuclear accumulation of the β-catenin, as shown by Western blot and immunofluorescence analysis. Moreover, fluoride also induced the expression of Wnt-targeted gene runt-related transcription factor 2 (Runx2). Importantly, the positive effect of fluoride on ALP activity and mRNA expressions of COL1A1, ALP, osteonection and Runx2 was abolished by DKK-1, a blocker of the Wnt/β-catenin receptor. Taken together, these findings suggest that fluoride promotes osteoblastic differentiation through Akt- and GSK-3β-dependent activation of Wnt/β-catenin signaling pathway in primary rat osteoblasts. Our findings provide novel insights into the mechanisms of action of fluoride in osteoblastogenesis.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Pan L,Shi X,Liu S,Guo X,Zhao M,Cai R,Sun Gdoi
10.1016/j.toxlet.2013.11.029subject
Has Abstractpub_date
2014-02-10 00:00:00pages
34-42issue
1eissn
0378-4274issn
1879-3169pii
S0378-4274(13)01444-6journal_volume
225pub_type
杂志文章abstract::Diclofenac is a widely prescribed NSAID that causes severe idiosyncratic drug induced liver injury (IDILI) in a small part of the patient population. Formation of protein-reactive metabolites is considered to play a role in the development of diclofenac-induced IDILI. Therefore, a high hepatic activity of enzymes invo...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.05.015
更新日期:2016-07-25 00:00:00
abstract::To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard IS...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.09.012
更新日期:2016-11-16 00:00:00
abstract::Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N-acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human keratinocyte cell line (HaCaT) and used GSH and NAC to cou...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.09.002
更新日期:2016-02-26 00:00:00
abstract::The chronic toxic effects of chromium (2.6 mg/1) on the carbohydrate metabolism of a teleost fish, Channa punctatus were examined after 60 and 120 days of exposure. After 60 days the lactic acid content of blood and muscles was increased but liver lactic acid content decreased. Liver glycogen was also depleted. The ac...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90003-6
更新日期:1983-04-01 00:00:00
abstract::Carbon nanotubes (CNT), despite their diverse application potential, have demonstrated adverse impacts in vitro and in vivo. Previous studies have focused on the combined in vitro cytotoxic impact of CNT aggregates and associated nanoparticulate impurities. However, the isolated effect of CNT aggregates and associated...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2006.12.003
更新日期:2007-02-28 00:00:00
abstract::Oxime-based acetylcholinesterase reactivators (briefly oximes) regenerate organophosphate-inactivated acetylcholinesterase and restore its function. Poor blood-brain-barrier passage and fast elimination from blood limit their actual use in treatment of patients exposed to organophosphates. Previous in vitro results im...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.11.021
更新日期:2020-03-01 00:00:00
abstract::The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most potent risk factor among tobacco-related carcinogens in lung cancer progression and outcomes. Although genetic mutations and chromosome instability have been detected in NNK-induced lung tumors, the oncogenic mechanisms o...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.09.019
更新日期:2017-11-05 00:00:00
abstract::The present study investigated the effects of in vitro methylmercury (MeHg) exposure on endogenous dopamine (DA) efflux from mouse striatal slices. MeHg produced a concentration-dependent increase in the spontaneous efflux of DA which was independent of the availability of Ca2+ in the superfusion medium. The Ca(2+)-de...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(96)03787-3
更新日期:1996-12-01 00:00:00
abstract::Behavioral endpoints offer special challenges to toxicology. One arises from the sometimes conflicting ways in which adverse effects may be expressed. For example, both increases and decreases in response rates of schedule-controlled performance may be produced by a specific agent, depending on the specific schedule. ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(88)90034-3
更新日期:1988-10-01 00:00:00
abstract::Cynomolgus monkeys showed no measurable adverse effects following inhalation of 500 ppm dimethylformamide (DMF), 6 h/d, 5 d/wk, for 2 weeks either when exposed whole-body or head-only (one monkey per exposure route). Measurement of DMF concentrations into and out of the head-only exposure unit along with measurement o...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(91)90076-i
更新日期:1991-12-01 00:00:00
abstract::About two decades ago in vitro mutagenicity tests were adopted as the first in vitro methods in regulatory toxicology. For reasons of animal welfare and better science, many validation studies of various in vitro methods were performed between 1985 and 1995 for their potential to replace the Draize eye irritation test...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/s0378-4274(01)00492-1
更新日期:2002-02-28 00:00:00
abstract::Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(91)90047-a
更新日期:1991-11-01 00:00:00
abstract::Short-term exposure to elevated levels of particulate matter is associated with increased respiratory and cardiovascular mortality and morbidity. However, the mechanisms underlying these effects are still unclear. Recent studies have suggested that inhaled ultrafine particles are able to translocate into the bloodstre...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2007.09.006
更新日期:2008-01-04 00:00:00
abstract::Superparamagnetic iron oxide nanoparticles (SPION) are used as high-sensitive enhancer for magnetic resonance imaging, where they represent a promising tool for early diagnosis of destructive diseases such as rheumatoid arthritis (RA). Since we could demonstrate that professional phagocytes are activated by amino-poly...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.01.003
更新日期:2016-03-14 00:00:00
abstract::Neurobehavioral effects of polychlorinated biphenyls (PCBs) at environmental levels of exposure have been reported in cross-sectional and prospective studies in infants and children. However, observations differ for effect spectrum, persistence and effective matrix (cord plasma, maternal plasma or milk). In order to i...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(98)00334-8
更新日期:1998-12-28 00:00:00
abstract::Human fetuses and neonates are particularly vulnerable to methylmercury (MeHg)-induced brain damage and are sensitive even to low exposure levels. Previous work of our group evidence that prenatal exposure to MeHg causes cognitive and behavioral alterations and disrupt hippocampus signaling. The current study aimed to...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.12.006
更新日期:2018-03-01 00:00:00
abstract::Apoptosis has been described as programmed active cell death. Overexpression of the c-Myc gene has been shown to induce apoptosis in Rat1A/Myc-ER cells when combined with a growth blocking agent. In the present study, we tested whether 4-Hydroxynonenal (HNE) or N-acetyl-L-cysteine (LNAC) affect apoptotic death in seru...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(96)03816-7
更新日期:1996-12-31 00:00:00
abstract::Humans are typically exposed to mixtures of substances, whereby their bioactivity can be significantly altered by co-occurring compounds. Thus, over the last years, research on combinatory effects has gained increasing attention. In particular, several xenoestrogens have been recently reported to interact synergistica...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2019.10.025
更新日期:2020-02-01 00:00:00
abstract::The direct or indirect interference with GABA-mediated neurotransmission results in convulsive seizure activity in humans and experimental animals. When this convulsant effect is experimentally analyzed, it turns out to be a product of discrete and restricted cerebral sites of drug action. Depending upon the brain cir...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(92)90215-6
更新日期:1992-12-01 00:00:00
abstract::Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. We examined whether variations in genes involved in base-excision (hOGG1, XRCC1) and double strand break (XRCC3) DNA repair contribute to inter-individual differences in genotoxic effects induced in ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.12.002
更新日期:2005-04-10 00:00:00
abstract::Benzene is a common occupational hazard and a ubiquitous environmental pollutant. Benzene exposure at the levels even below 1ppm still showed hematotoxicity. It is widely accepted that the metabolites of benzene play important roles in the benzene toxicity to the hematopoietic system, but little is known about the eff...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2011.03.012
更新日期:2011-06-24 00:00:00
abstract::The role of intra- and extracellular calcium in the activation of human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM) were studied by using soluble, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), or particulate stimuli, quartz or chrysotile. A calciu...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(95)03255-j
更新日期:1995-08-01 00:00:00
abstract::Cadmium (Cd) occurs naturally in the environment and the general population's exposure to it is predominantly through diet. Chronic Cd exposure is a public health concern because Cd is a known carcinogen; it accumulates in the body and causes kidney damage. The National Health and Nutritional Examination Survey (NHANE...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2010.04.022
更新日期:2010-09-15 00:00:00
abstract::Toluene diisocyanate (TDI), a highly reactive industrial chemical is a leading cause of occupational asthma in westernized countries. It has also been reported to be a skin sensitizer in mice and guinea pigs although instances of skin sensitivity in humans are rare. It is uncertain if skin-contact is necessary to init...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00325-3
更新日期:2001-04-08 00:00:00
abstract::An intensive study was conducted to provide data on intra- and inter-individual variation in urinary excretion of a series of ingredients in personal care products (parabens, triclosan, benzophenones) and bisphenol A (BPA, not expected to be an ingredient) in 8 volunteers over 6 days. Exposure diaries recorded use of ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.06.023
更新日期:2014-12-01 00:00:00
abstract::Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to investigate the possibility of oxidative stress induction by cypermethrin, a Type II pyrethroid. Either single (170 mg/kg) or repeated (75 mg/kg per day for 5 days) or...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00277-0
更新日期:2001-01-03 00:00:00
abstract::Caloric restriction is known to reduce chemically-induced tumor incidence in laboratory animals. The effect is believed to be mediated in part by modification of hepatic drug metabolism, including both phase I and phase II enzymes. Using aflatoxin B1 (AFB1) as a model carcinogen, we studied the effect of caloric restr...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(92)90150-i
更新日期:1992-07-01 00:00:00
abstract::We have recently demonstrated that the antibody response to the T-cell-dependent antigen, sheep red blood cells (SRBCs), was suppressed by ethyl carbamate in female BALB/c mice. At the same doses, ethyl carbamate decreased in the numbers of splenic macrophages, B cells, total T cells, CD4(+) T cells and CD8(+) T cells...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00306-4
更新日期:2001-03-08 00:00:00
abstract::Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have on...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2015.11.023
更新日期:2016-01-22 00:00:00
abstract::Groups of people with no occupational exposure to Br-containing chemicals (29-54 year old, mostly women) in Japan, China and Korea, respectively, offered spot urine samples. Those in China and Korea offered 24 h duplicates of foods of the day. Urine samples were analyzed for Br by ECD-gas chromatography (ECD-GC) after...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(02)00192-3
更新日期:2002-08-05 00:00:00